한빛사논문
- 조회304
Nandin Mandakhbayar a,b,1, YunSeong Ji a,b,1, Ahmed El-Fiqi c, Kapil D. Patel a,b,d, Dong Suk Yoon a,e, Khandmaa Dashnyam a,b,f, Oyunchimeg Bayaraa a,b,f, Gangshi Jin a,b, Khaliunsarnai Tsogtbaatar a,b,f, Tae-Hyun Kim a,b,g, Jung-Hwan Lee a,b,h,i,j,k, Hae-Won Kim a,b,h,i,j,k
aInstitute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea
bDepartment of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea
cGlass Research Department, National Research Centre, Cairo, 12622, Egypt
dSchool of Cellular and Molecular Medicine (CMM), University of Bristol, Bristol, BS8 1TD United Kingdom
eDepartment of Biomedical Science, Hwasung Medi-Science University, Hwaseong‑Si 18274, Gyeonggi‑Do, Republic of Korea
fDrug Research Institute, Mongolian University of Pharmaceutical Sciences, Ulaanbaatar 14250, Mongolia
gR&D Center, TE Bios, Osong, Republic of Korea
hDepartment of Biomaterials Science, School of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea
iMechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea
jUCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea
kCell & Matter Institute, Dankook University, Cheonan 31116, Republic of Korea
1These authors contributed equally to this work.
Corresponding authors: Jung-Hwan Lee, Hae-Won Kim
Abstract
Regeneration of pathological wounds, such as diabetic ulcers, poses a significant challenge in clinical settings, despite the widespread use of drugs. To overcome clinical side effects and complications, drug-free therapeutics need to be developed to promote angiogenesis while overcoming inflammation to restore regenerative events. This study presents a novel bioactive nanozyme based on cobalt-doped nanoglass (namely, CoNZ), which exhibits high enzymatic/catalytic activity while releasing therapeutic ions. Cobalt oxide “Co3O4” tiny crystallites produced in situ through a chemical reaction with H2O2 within CoNZ nanoparticles play a crucial role in scavenging ROS. Results showed that CoNZ-treatment to full-thickness skin wounds in mice significantly accelerated the healing process, promoting neovascularization, matrix deposition, and epithelial lining while reducing pro-inflammatory signs. Notably, CoNZ was highly effective in treating pathological wounds (streptozotocin-induced diabetic wounds). Rapid scavenging of ROS by CoNZ and down-regulation of pro-inflammatory markers while up-regulating tissue healing signs with proliferative cells and activated angiogenic factors contributed to the observed healing events. In vitro experiments involving CoNZ-cultures with macrophages and endothelial cells exposed to high glucose and ROS-generating conditions further confirmed the effectiveness of CoNZ. CoNZ-promoted angiogenesis was attributed to the release of cobalt ions, as evidenced by the comparable effects of CoNZ-extracted ionic medium in enhancing endothelial migration and tubule formation via activated HIF-1α. Finally, we compared the in vivo efficacy of CoNZ with the clinically-available drug deferoxamine. Results demonstrated that CoNZ was as effective as the drug in closing the diabetic wound, indicating the potential of CoNZ as a novel drug-free therapeutic approach.
논문정보
- Research article
- 2023년 08월 (BRIC 등록일 2023-09-07)
- 국내(교신)+국외 연구진
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